TY - JOUR
KW - Angiotensin-Converting Enzyme 2
KW - Animals
KW - Betacoronavirus
KW - Blood Vessels
KW - COVID-19
KW - Chlorocebus aethiops
KW - Coronavirus Infections
KW - Humans
KW - kidney
KW - Mice
KW - organoids
KW - Pandemics
KW - Peptidyl-Dipeptidase A
KW - Pneumonia, Viral
KW - Receptors, Virus
KW - Recombinant Proteins
KW - SARS-CoV-2
KW - Spike Glycoprotein, Coronavirus
KW - Vero Cells
KW - angiotensin converting enzyme 2
KW - Blood Vessels
KW - human organoids
KW - kidney
KW - severe acute respiratory syndrome coronavirus
KW - spike glycoproteins
KW - treatment
AU - Vanessa Monteil
AU - Hyesoo Kwon
AU - Patricia Prado
AU - Astrid Hagelkrüys
AU - Reiner A. Wimmer
AU - Martin Stahl
AU - Alexandra Leopoldi
AU - Elena Garreta
AU - Carmen Hurtado Del Pozo
AU - Felipe Prosper
AU - Juan Pablo Romero
AU - Gerald Wirnsberger
AU - Haibo Zhang
AU - Arthur S. Slutsky
AU - Ryan Conder
AU - Nuria Montserrat
AU - Ali Mirazimi
AU - Josef M. Penninger
AB - We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000-5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.
BT - Cell
DA - 2020-05-14
DO - 10.1016/j.cell.2020.04.004
IS - 4
LA - eng
N2 - We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000-5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.
PY - 2020
SP - 905
EP - 913.e7
T2 - Cell
TI - Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2
VL - 181
SN - 1097-4172
ER -